Anxiety Cells' Identified in the Brain's Hippocampus

Do your palms sweat when you walk down a poorly lit street at night? That feeling may be traced to the firing of newly identified “anxiety” cells deep inside your brain, according to research published in the journal Neuron.

The researchers found the cells in the brains of mice, inside a structure called the hippocampus. But the cells probably also exist in humans, says one of the study’s senior investigators.

“We call these anxiety cells because they only fire when the animals are in places that are innately frightening to them,” author says. “For a mouse, that’s an open area where they’re more exposed to predators, or an elevated platform.”

The firing of the anxiety cells sends messages to other parts of the brain that turn on anxious behaviors; in mice, those include avoiding the dangerous area or fleeing to a safe zone.

Though many other cells in the brain have been identified as playing a role in anxiety, the cells found in this study are the first known to represent the state of anxiety, regardless of the type of environment that provokes the emotion.

Using freely moving calcium imaging and optogenetics, authors show that while the dorsal CA1 subregion of the hippocampus is enriched in place cells, ventral CA1 (vCA1) is enriched in anxiety cells that are activated by anxiogenic environments and required for avoidance behavior. Imaging cells defined by their projection target revealed that anxiety cells were enriched in the vCA1 population projecting to the lateral hypothalamic area (LHA) but not to the basal amygdala (BA).

Consistent with this selectivity, optogenetic activation of vCA1 terminals in LHA but not BA increased anxiety and avoidance, while activation of terminals in BA but not LHA impaired contextual fear memory.

“This is exciting because it represents a direct, rapid pathway in the brain that lets animals respond to anxiety-provoking places without needing to go through higher-order brain regions,” says the study’s other senior investigator.

Anxiety is normal and critical to an animal’s safety. Anxiety is an emotional response to a distant threat—being in an environment that exposes an animal to predators, for example. The safe bet is to sidestep those environments, so anxiety kicks in avoidance behaviors.

When people overestimate threats—when talking to a crowd invokes the same response as potentially running into a snake—anxiety becomes a problem.

To understand how things go awry in anxiety disorders, researchers have been looking at mice to decipher how the brain processes healthy anxiety.

The hippocampus plays a well-known role in the brain’s ability to form new memories and to help animals—from mice to humans—navigate through complex environments. But recent research has also implicated the hippocampus in regulating mood, and studies have shown altering brain activity in the ventral part of the hippocampus can reduce anxiety. It’s also known that the hippocampus sends signals to other areas of the brain—the amygdala and the hypothalamus—that have also been shown to control anxiety-related behavior.